BMC Medicine最新文献

Background: Over the past decades, the prevalence of obesity among adults has rapidly increased, particularly in socioeconomically deprived urban neighbourhoods. To better understand the complex mechanisms behind this trend, we created a system map exposing the underlying system driving obesity prevalence in socioeconomically deprived urban neighbourhoods over the last three decades in the Netherlands.

Methods: We conducted Group Model Building (GMB) sessions with a group of thirteen interdisciplinary experts to develop a Causal Loop Diagram (CLD) of the obesogenic system. Using system-based analysis, the underlying system dynamics were interpreted.

Results: The CLD demonstrates the food environment, physical activity environment, socioeconomic environment and socio-political environment, and their interactions. We identified the following overarching reinforcing dynamics in the obesogenic system in socioeconomically deprived urban neighbourhoods: (1) adverse socioeconomic conditions and an unhealthy food environment reinforced each other, (2) increased social distance between social groups and adverse socioeconomic conditions reinforced each other and (3) increased social distance between institutions and communities and the normalisation of unhealthy behaviours reinforced each other. These deeper system dynamics further reinforced chronic stress, sedentary behaviour, sleeping problems, unhealthy diets and reduced physical activity over time. In turn, these dynamics led to the emergent result of rising obesity prevalence in socioeconomically deprived urban neighbourhoods over the past decades.

Conclusions: Our study sheds light on the system dynamics leading to neighbourhoods with an unhealthy food environment, challenging socioeconomic conditions, a widening distance between social groups and an infrastructure that discouraged physical activity while promoting sedentary behaviour. Our insights can form the basis for the development of an integrated approach aimed at reshaping the obesogenic system in socioeconomically deprived urban neighbourhoods.

Background: Maternal stress is a potential factor affecting fetal growth, but it is unknown whether it directly affects fetal growth restriction. This study aims to investigate the association between pre-pregnancy maternal stress with small for gestational age (SGA).

Methods: This study used a population-based retrospective cohort analysis to examine the association between pre-pregnancy maternal stress and SGA in offspring. Data were extracted from the National Preconception Health Care Project (NPHCP), conducted between 2010 and 2012, which encompassed preconception health-related information from 572,989 individuals across various regions in China. Logistic regression models were used to assess the associations between pre-pregnancy maternal stress variables and the risk of SGA. In addition, Synthetic Minority Over-sampling Technique (SMOTE) and Propensity Scores (PS) methods were used to enhance the model's ability to the associations between pre-pregnancy maternal stress and SGA.

Results: Pre-pregnancy maternal stress was significantly associated with an increased the risk of SGA in offspring (OR 1.35, 95% CI 1.20 to 1.51, P < 0.001). Stress related to life and economic factors notably increased the risk of SGA across different socio-economic conditions, whereas stress related to friends did not show a statistically significant association (P > 0.05). Specially, individuals with lower socio-economic status that characterized by below high school education levels (OR = 1.45, 95% CI: 1.23 to 1.70), farmer occupation (OR = 1.33, 95% CI: 1.15 to 1.55, P = 0.002), rural residence (OR = 1.38, 95% CI: 1.22 to 1.56, P < 0.001), and younger age (under 35 years: OR = 1.35, 95% CI: 1.20 to 1.52, P < 0.001) were more susceptible to pre-pregnancy maternal stress, increasing their risk of SGA.

Conclusions: Pre-pregnancy maternal stress was positively associated with an increased risk of SGA in offspring. Individuals with lower socio-economic status were more likely to experience pre-pregnancy maternal stress related to life and economic factors, which in turn contributed to a higher risk of SGA.

Background: We aimed to identify specific multimorbidity latent classes among multi-ethnic community-dwelling adults aged ≥ 18 years in Malaysia. We further explored the risk factors associated with these patterns and examined the relationships between the multimorbidity patterns and 11-year all-cause mortality risk, as well as health-related quality of life (HRQoL).

Methods: Using data from 18,101 individuals (aged 18-97 years) from the baseline Census 2012, Health Round 2013, and Verbal Autopsies 2012-2023 of the South East Asia Community Observatory (SEACO) health and demographic surveillance system, latent class analysis was performed on 13 chronic health conditions to identify statistically and clinically meaningful groups. Multinomial logistic regression and Cox proportional hazards regression models were conducted to investigate the adjusted association of multimorbidity patterns with the risk factors and mortality, respectively. HRQoL was analyzed by linear contrasts in conjunction with ANCOVA adjusted for baseline confounders.

Results: Four distinct multimorbidity latent classes were identified: (1) relatively healthy (n = 10,640); (2) cardiometabolic diseases (n = 2428); (3) musculoskeletal, mobility and sensory disorders (n = 2391); and (4) complex multimorbidity (a group with more severe multimorbidity with combined profiles of classes 2 and 3) (n = 699). Significant variations in associations between socio-demographic characteristics and multimorbidity patterns were discovered, including age, sex, ethnicity, education level, marital status, household monthly income and employment status. The complex multimorbidity group had the lowest HRQoL across all domains compared to other groups (p < 0.001), including physical health, psychological, social relationships and environment. This group also exhibited the highest mortality risk over 11 years even after adjustment of confounders (age, sex, ethnicity, education and employment status), with a hazard of death of 1.83 (95% CI 1.44-2.33), followed by the cardiometabolic group (HR 1.42, 95% CI 1.18-1.70) and the musculoskeletal, mobility and sensory disorders group (HR 1.29, 95% CI 1.04-1.59).

Conclusions: Our study advances the understanding of the complexity of multimorbidity and its implications for health outcomes and healthcare delivery. The findings suggest the need for integrated healthcare approaches that account for the clusters of multiple conditions and prioritize the complex multimorbidity cohort. Further longitudinal studies are warranted to explore the underlying mechanisms and evolution of multimorbidity patterns.

Ovarian cancer remains the most lethal gynecological malignancy. Despite the approval of promising targeted therapy such as bevacizumab and PARP inhibitors, 5-year survival has not improved significantly. Thus, there is an urgent need for new therapeutics. New advancements in therapeutic strategies target the pivotal hallmarks of cancer. This review is giving an updated overview of innovative and upcoming therapies for the treatment of ovarian cancer that focuses specific on the hallmarks of cancer. The hallmarks of cancer constitute a broad concept to reenact complexity of malignancies and furthermore identify possible targets for new treatment strategies. For this purpose, we analyzed approvals and current clinical phase III studies (registered at ClinicalTrials.gov (National Library of Medicine, National Institutes of Health; U.S. Department of Health and Human Services, 2024)) for new drugs on the basis of their mechanisms of action and identified new target approaches. A broad spectrum of new promising drugs is currently under investigation in clinical phase III studies targeting mainly the hallmarks "self-sufficiency in growth signals," "genomic instability," and "angiogenesis." The benefit of immune checkpoint inhibitors in ovarian cancer has been demonstrated for the first time. Besides, targeting the tumor microenvironment is of growing interest. Replicative immortality, energy metabolism, tumor promoting inflammation, and the microbiome of ovarian cancer are still barely targeted by drugs. Nevertheless, precision medicine, which focuses on specific disease characteristics, is becoming increasingly important in cancer treatment.

Background: Patients with systemic lupus erythematosus (SLE) suffered from an increasing risk of cardiovascular diseases. In this multi-center prospective study, we aimed to determine the association between antiphospholipid antibodies (aPLs) and future atherosclerotic cardiovascular disease (ASCVD) in SLE.

Methods: In total, 1573 SLE patients were recruited based on the Chinese SLE Treatment and Research group (CSTAR) registry. aPLs profile, including anticardiolipin antibodies (aCL) IgG/IgM, anti-β2 glycoprotein I antibodies (aβ2GPI) IgG/IgM, and lupus anticoagulant (LA), were measured in each center. Future ASCVD events were defined as new-onset myocardial infarction, stroke, artery revascularization, or cardiovascular death.

Results: Among the 1573 SLE patients, 525 (33.4%) had positive aPLs. LA had the highest prevalence (324 [20.6%]), followed by aCL IgG (249 [15.8%]), aβ2GPI IgG (199 [12.7%]). 116 (7.37%) patients developed ASCVD during the mean follow-up of 4.51 ± 2.32 years and 92 patients were aPLs positive. In univariate Cox regression analysis, both aPLs (HR = 7.81, 95% CI 5.00-12.24, p < 0.001) and traditional risk factors of cardiovascular disease were associated with future ASCVD events. In multiple Cox regression analysis, aCL IgG (HR = 1.95, 95% CI 1.25-3.00, p = 0.003), aCL IgM (HR = 1.83, 95% CI 1.03-3.20, p = 0.039), and LA (HR = 5.13, 95% CI 3.23-8.20, p < 0.001) positivity remained associated with ASCVD; traditional risk factors for ASCVD, including smoking, gender, age and hypertension, also play an independent role in SLE patients. More importantly, Aspirin can reduce ASCVD risk in SLE patients with positive aPLs (HR = 0.57 95% CI, 0.25-0.93, P = 0.026).

Conclusions: SLE patients with positive aPLs, especially positive aCL IgG/IgM and LA, warrant more care and surveillance of future ASCVD events during follow-up. Aspirin may have a protective effect on future ASCVD.

Background: Obesity particularly during childhood is considered a global public health crisis and has been linked with later life health consequences including mental health. However, there is lack of causal understanding if childhood body size has a direct effect on mental health or has an indirect effect after accounting for adulthood body size.

Methods: Two-sample Mendelian randomization (MR) was performed to estimate the total effect and direct effect (accounting for adulthood body size) of childhood body size on anxiety and depression. We used summary statistics from a genome-wide association study (GWAS) of UK Biobank (n = 453,169) and large-scale consortia of anxiety (Million Veteran Program) and depression (Psychiatric Genomics Consortium) (n = 175,163 and n = 173,005, respectively).

Results: Univariable MR did not indicate genetically predicted effects of childhood body size with later life anxiety (beta = - 0.05, 95% CI = - 0.13, 0.02) and depression (OR = 1.06, 95% CI = 0.94, 1.20). However, using multivariable MR, we observed that the higher body size in childhood reduced the risk of later life anxiety (beta = - 0.19, 95% CI = - 0.29, - 0.08) and depression (OR = 0.83, 95% CI = 0.71, 0.97) upon accounting for the effect of adulthood body size. Both univariable and multivariable MR indicated that higher body size in adulthood increased the risk of later life anxiety and depression.

Conclusions: Higher body size in adulthood may increase the risk of anxiety and depression, independent of childhood higher body size. In contrast, higher childhood body size does not appear to be a risk factor for later life anxiety and depression.

Background: The benefits of intravenous thrombolysis in patients with acute minor stroke remain controversial. For the aim of providing a better therapeutic strategy, high-quality trials are required to validate the efficacy of thrombolytic medicine other than intravenous recombinant tissue plasminogen and tenecteplase. In the trial, we evaluate the efficacy and safety of urokinase (UK) in acute minor stroke.

Methods: This multicenter, open-label, blinded-endpoint, randomized controlled clinical trial enrolled patients with minor stroke within 6 h of symptom onset, with a NIHSS score ≤ 5. The trial was conducted at 25 hospitals in China between October 2020 and February 2023. Eligible patients were randomized to the UK group (1,000,000 U) or the best medicine treatment group. The responsible investigator recommended and implemented the best medicine treatment based on guidelines. The primary endpoint was an excellent functional outcome, defined as a modified Rankin scale (mRS) score of 0-1 at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) within 36 h.

Results: A total of 999 patients were enrolled in the trial, the median age was 64 years, 371 (36.9%) were women; the median (IQR) NIHSS score was 3 (2-4). At 90 days, the primary endpoint was observed in 427 patients (84.9%) in the UK group and 425 patients (85.7%) in the control group (adjusted risk ratio [RR] 1.00, 95% CI 0.96-1.05, p = 0.87). A total of 3 patients in the UK-treated (0.6%) group experienced sICH compared to 1 patient (0.2%) in the control group (RR 1.83, 95% CI 0.16-20.27, p = 0.62).

Conclusions: For patients with acute minor stroke treated within 6 h of symptom onset, UK intravenous thrombolysis treatment was not found to be beneficial in terms of excellent functional outcome at 90 days, whereas it was safe.

Trial registration: ClinicalTrials.gov Identifier: NCT04420351.

Background: Lung cancer is a leading cause of cancer-related mortality. Non-small cell lung cancer (NSCLC) comprises 85% of cases with rising incidence among never-smokers (NS). This study seeks to compare clinical, imaging, pathology, and outcomes between NS and ever-smokers (S) NSCLC patients to identify significant differences if any.

Methods: Retrospective cohort study of 155 NSCLC patients (88 S and 67 NS). The main predictor was smoking. Clinical, imaging, and pathology findings were evaluated at initial biopsy for staging. The primary outcome was all-cause mortality, and the secondary outcome was 12-month progression-free survival.

Results: Imaging: NS and S had similar nodule size (0.81), calcification (> 0.99), and invasion of adjacent structures (> 0.99) (p values). NS slightly trended to more commonly involve the RLL vs S the RUL (p = 0.11). NS had higher numbers of extrathoracic metastases at initial biopsy for staging (p = 0.055).

Pathology: NS more commonly had adenocarcinoma compared to S, who had equal numbers of adenocarcinoma and squamous cell carcinoma (p = 0.001). Rates of lymphovascular and pleural invasion were similar (p = 0.84 and 0.28). Initial staging: NS were more often initially diagnosed with stage IV disease (p = 0.046), positive nodal disease (p = 0.002), and metastatic disease (p = 0.004).

Outcomes: S had a non-significant trend toward worse 12-month progression-free survival (rate ratio = 1.31, p = 0.31; HR = 1.33, p = 0.28). NS and S had similar 1-year all-cause mortality (HR = 1.06, p = 0.90). S had nearly double the risk of all-cause mortality in 5 years (HR = 1.73, p = 0.056) and 10 years (HR = 1.77, p = 0.02). Median survival was 6.6 years for NS and 3.9 years for S, with NS surviving 2.7 years longer on average (p = 0.045).

Conclusions: CT nodule features were similar in NS and S. NS more often had metastatic adenopathy, distant metastases, and stage IV disease at initial biopsy. Despite similar 12-month progression-free survival and 1-year all-cause mortality, S had nearly double the risk of mortality in the first 5 and 10 years post-diagnosis.

Trial registration: Retrospectively registered.

Background: The proliferation capacity of adult cardiomyocytes is very limited in the normal adult mammalian heart. Previous studies implied that cardiomyocyte proliferation increases after injury stimulation, but the result is controversial partly due to different methodologies. We aim to evaluate whether myocardial infarction (MI) stimulates cardiomyocyte proliferation in adult mice.

Methods: A comprehensive literature search was conducted through PubMed/Medline, Embase, and Web of Science databases from 1 January 2000 to 21 December 2023. The SYRCLE's Risk of Bias tool for animal experiments was used to evaluate the quality of the literature by two independent reviewers. Twenty-six studies with cell cycle indicators (Ki67⁺, PH3⁺, BrdU/EdU⁺, and AurkB⁺) to evaluate cycling cardiomyocytes were collected for a meta-analysis. Another 10 studies with genetic reporter/tracing systems to evaluate cardiomyocyte proliferation were collected for a systematic review.

Results: Evaluating cardiomyocyte proliferation by immunostaining of the cell cycle indicators on heart tissue, the meta-analysis showed that differences of Ki67⁺, PH3⁺, and BrdU/EdU⁺ cycling cardiomyocytes between MI and Sham groups were not statistically significant. In the post-MI heart, the percentages of PH3⁺, BrdU/EdU⁺, and AurkB⁺ cardiomyocytes were not significantly different between the infarct border zone and remote zone. The percentage of Ki67⁺ cardiomyocytes in the infarct border zone was statistically higher than that in the remote zone. Most of the studies (6 out of 10) using genetic reporter/tracing mouse systems showed that the difference in cardiomyocyte proliferation between MI and Sham groups was not statistically significant. Among the other 4 studies, at least 3 studies could not demonstrate that MI stimulates bona fide cardiomyocyte proliferation because of methodological shortages.

Conclusions: MI injury increases Ki67⁺ cycling adult mouse cardiomyocytes in infarct border zone. Very little overwhelming evidence shows that MI stimulates bona fide proliferation in the adult heart.